Factors influencing the acid-base changes in the air-pouch exudate following carrageenan induced inflammation in rats

Abstract

The interactions between the acid-base variables that contribute to exudate acidosis were studied in the subcutaneous air-pouch after carrageenan injection in rats. We studied the concurrent changes of exudate gases (PCO2 and PO2), main ions ([Na+], [K+], [Ca2+], [Mg2+], [Cl-] and [Lac-]), inorganic phosphate (P(i)) and albumin in acutely inflamed rats (4, 8, 12, 24 and 48 h of inflammation). A notable hypercapnia was found in the exudate after only 8 h (exudate PCO2 = 64.3 +/- 2.9 mm Hg) but this hypercapnia decreased after 48 h (32.9 +/- 12.7 mm Hg), coincident with the greatest increase in exudate cells. With respect to the metabolic acid-base variables, the most important changes found were a parallel decrease in the strong ion difference ([SID]) and exudate pH, as well as increases in the exudate weak acid buffers ([ATOT]) due to albumin and inorganic phosphate (P(i)) increases. However, after 12 h, the exudate acidosis was stable at around pH 7. A similar acid pH was obtained after 24 h of inflammation when the carrageenan solution injected was previously adjusted to a physiological pH (7.4). This pH, analogous to that of the exudate, was the result of compensation by the acid-base independent variables, a fact which suggests that acid pH may be a beneficial condition for cells taking part in inflammatory processes.

Extracellular pH affects inflammatory cell production of superoxide and nitric oxide

“…The infiltration of large number of cells, requiring 02 to live and to support their phagocytic functions, may explain these values. We have previously described the ionic shifts and other factors influencing the acid-base changes of the exudate induced by carrageenan (5). Our present results show that pH stabilized at around 7 after 12h of inflammation and remained at that level for up to 48 h. The low pH accompanied by low PCOz values at 48 h indicates that acidity was due to metabolic acid load at the inflammation site.…”

“…Phagocytes are routinely incubated in vitro in a culturing environment with buffers at pH 7.4 (1, 3). Due to the low pH reported in the synovial fluid of rheumatoid knees (4) and in the exudate from inflamed rats (5), the question arises as to whether an acidic environment can affect the release of such radicals. The granuloma-pouch model induced by carrageenan was chosen due to its histological similarity with human inflammatory joint diseases (6).…”

Dexamethasone lowers cytosolic pH in macrophages by altering alkalinizing pH-regulatory mechanisms

“…Furthermore, a mobilization of H ϩ -ATPase from intracellular stores to the plasma membrane has been suggested to occur in cells from turtle bladder [32], medullary collecting duct cells [33], and in neutrophils [34], but such a mechanism has not yet been demonstrated in macrophages. At the low pH of an inflammatory lesion, phagocyte function could depend upon ATP-dependent extrusion of protons because other pH-regulatory mechanisms, like the Na ϩ /H ϩ -exchanger and the HCO 3 Ϫ -dependent exchangers, would be inhibited due to unfavorable proton and bicarbonate gradients [2,8].…”

“…Altered recovery from an acid load in Na/HCO 3 medium was demonstrated and the pH levels after 20 min of pH recovery differed with and without dexamethasone treatment. However, at a reduced pH e of an inflammatory lesion, the activity of the Na ϩ -dependent Cl Ϫ /HCO 3 Ϫ exchanger would tend to be inhibited due to a reduced bicarbonate content [2]. The proton pump is therefore more likely to be responsible for any difference in pH c caused by dexamethasone at acidic pH e becaue it is fueled by ATP and possibly less sensitive to external acidification.…”

“…Furthermore, by their ability to secrete various substances they affect other cell types, and macrophage-derived products have been implicated in pathological processes such as atherosclerosis and rheumatoid arthritis [1]. At an inflammatory site, macrophages are exposed to a variable environment (pH, nutritional status, oxygenation) in which they must defend and maintain a closely regulated cytosolic pH (pH c ) [2]. This is in part accomplished by a tight regulation of plasma membranelocalized alkalinizing and acidifying mechanisms.…”